The effect of N-[(trans-4-isopropylcyclohexyl)-carbonyl]-D-phenylalanine (A-4166) on nutrient metabolism was investigated in isolated rat pancreatic islets. 2. At a 10-microM concentration, the meglitinide analogue caused a modest increase in 14CO2 output from islets prelabeled with L-[U-14C]glutamine but failed to affect D-[5-3H]glucose utilization, D-[U-14C]glucose oxidation and conversion into 14C-labeled acidic metabolites and amino acids, L[1-14C]leucine and L-[U-14C]leucine oxidation, the generation of 2-ketoisocaproate and further acidic metabolites from the branched-chain amino acid and the production of 14CO2 by islets prelabeled with [U-14C]palmitate. 3. These findings indicate that the insulinotropic action of A-4166 is not attributable to any sizeable increase in the metabolism of exogenous or endogenous nutrients.
